Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma

Hongmei Nan, Mousheng Xu, Peter Kraft, Abrar A. Qureshi, Constance Chen, Qun Guo, Frank B. Hu, Gary Curhan, Christopher I. Amos, Li E. Wang, Jeffrey E. Lee, Qingyi Wei, David J. Hunter, Jiali Han

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Abstract

We conducted a genome-wide association study on cutaneous basal cell carcinoma (BCC) among 2045 cases and 6013 controls of European ancestry, with follow-up replication in 1426 cases and 4845 controls. A nonsynonymous SNP in the MC1R gene (rs1805007 encoding Arg151Cys substitution), a previously well-documented pigmentation gene, showed the strongest association with BCC risk in the discovery set (rs1805007[T]: OR (95% CI) for combined discovery set and replication set [1.55 (1.45-1.66); P = 4.3 × 10 -17]. We identified that an SNP rs12210050 at 6p25 near the EXOC2 gene was associated with an increased risk of BCC [rs12210050[T]: combined OR (95% CI), 1.24 (1.17-1.31); P = 9.9 × 10 -10]. In the locus on 13q32 near the UBAC2 gene encoding ubiquitin-associated domain-containing protein 2, we also identified a variant conferring susceptibility to BCC [rs7335046 [G]; combined OR (95% CI), 1.26 (1.18-1.34); P = 2.9 × 10 -8]. We further evaluated the associations of these two novel SNPs (rs12210050 and rs7335046) with squamous cell carcinoma (SCC) risk as well as melanoma risk. We found that both variants, rs12210050[T] [OR (95% CI), 1.35 (1.16-1.57); P = 7.6 × 10 -5] and rs7335046 [G] [OR (95% CI), 1.21 (1.02-1.44); P = 0.03], were associated with an increased risk of SCC. These two variants were not associated with melanoma risk. We conclude that 6p25 and 13q32 are novel loci conferring susceptibility to non-melanoma skin cancer.

Original languageEnglish (US)
Article numberddr287
Pages (from-to)3718-3724
Number of pages7
JournalHuman molecular genetics
Volume20
Issue number18
DOIs
StatePublished - Sep 1 2011

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Nan, H., Xu, M., Kraft, P., Qureshi, A. A., Chen, C., Guo, Q., Hu, F. B., Curhan, G., Amos, C. I., Wang, L. E., Lee, J. E., Wei, Q., Hunter, D. J., & Han, J. (2011). Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Human molecular genetics, 20(18), 3718-3724. [ddr287]. https://doi.org/10.1093/hmg/ddr287